Insulin Secretion Following Carbutamide Injections in Normal Dogs. ∗

Abstract

Summary and Conclusions

The mechanism of the hypoglycemic action of carbutamide in normal dogs was studied by means of pancreatic-femoral and mesenteric-femoral cross-circulation experiments. The results of these acute experiments suggest that: 1) carbutamide hypoglycemia is accompanied by secretion of insulin; 2) carbutamide does not cause degranulation or other significant changes in appearance of pancreatic A and B cells; 3) clearance of carbutamide from blood is relatively slow, as reported by others(21); 4) some dogs are refractory to the hypoglycemic action of carbutamide in doses of 50 mg/kg I.V. The results are consistent with the hypothesis that insulin secretion is one of the results of carbutamide action. The continued administration of carbutamide in animals and men with reduced pancreatic reserve may stimulate the islets of Langerhans to regeneration or to exhaustion. Although some evidence suggests that islet growth does occur (10,12), the second alternative has not been ruled out and should be investigated before the sulfonylureas can be recommended for the prolonged treatment of diabetes mellitus.